Purpose :
Inflammasomes are important components of innate immunity and have been shown to induce pyroptosis in cells by promoting the maturity of inflammatory cytokines interleukin-1β and interleukin-18. We have shown previously that mRNAs for the nucleotide-binding oligomerization domain-like receptors (NLR) family of inflammasomes are stimulated within MCMV-infected eyes during the progression of retinitis in mice with MAIDS [J Virol, 2012]. To begin to define with greater precision the relative roles of NLR inflammasomes during pathogenesis of MAIDS-related MCMV retinitis, we focused on the NLRP3 inflammasome and performed a series of in vivo studies to test the hypothesis that the NLRP3 inflammasome is involved in the development of retinal necrosis associated with MCMV retinitis in mice with MAIDS.

Methods :
The eyes of groups of NLRP3 inflammasome knockout mice with MAIDS and wildtype C57BL/6 mice with MAIDS were injected subretinally with MCMV. MCMV-infected eyes were collected 10 days later and subjected to either histopathologic analysis to determine frequency and severity of retinitis or standard plaque assay for quantification of infectious MCMV.

Results :
MCMV-infected eyes of NLRP3 knockout mice with MAIDS showed marked reduction in the severity and frequency of retinitis when compared with MCMV-infected eyes of wildtype mice with MAIDS despite no significant difference in the amounts of intraocular virus.

Conclusions :
That MCMV-infected eyes of NLRP3 knockout mice with MAIDS showed a marked reduction of frequency and severity of retinitis supports a role for NLRP3 inflammasomes in the pathogenesis of MAIDS-related MCMV retinitis. Studies are underway to determine if other NLR-subset inflammasomes are essential for the pathogenesis of MCMV retinitis.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.